The Treatment of Benign Prostatic Hyperplasia

FACULTY:

Nicholas R. Blanchard, PharmD, MEd
Professor and Dean School of Pharmacy
University of Maryland Eastern Shore
Princess Anne, Maryland

Asim M. Abu-Baker, PharmD
Assistant Professor,
Wegmans School of Pharmacy,
St. John Fisher College Rochester,
New York

FACULTY DISCLOSURE STATEMENTS:

Drs. Blanchard and Abu-Baker have no actual or potential conflicts of interest in relation to this program. U.S. Pharmacist does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy Postgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
Program No.: 430-000-08-016-H01-P; 430-000-08-016-H01-T
Credits: 2.0 hours (0.20 ceu)

TARGET AUDIENCE:

This accredited program is targeted to pharmacists and pharmacy technicians. Estimated time to complete this monograph and posttest is 90 to 120 minutes.

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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. GOAL: To give participants a good understanding of the etiology, manifestations, diagnosis, and treatment of benign prostatic hyperplasia (BPH).

OBJECTIVES:

Upon completion of this article, the pharmacist should be able to:

• Discuss BPH and why it occurs.*
• Explain the BPH Symptom Score Index and how it can be used to assess a patient’s improvement.*
• Describe the classes of medications used to treat BPH and how they work.*
• Recognize potential side effects of medications used to treat BPH.*

*Also applies to pharmacy technicians.

Benign prostatic hyperplasia (BPH) is the most commonly occurring benign neoplasm in aging American men. This condition may also be referred to as benign prostatic hypertrophy. The term benign prostatic hyperplasia is preferred, however, as it describes the epithelial-cell hyperplasia that is seen upon microscopic examination. By the age of 70, nearly 80% of men have some degree of BPH, which may cause a variety of bothersome urinary symptoms.¹

Overview

The prostate is a male accessory sexual gland that is responsible for a component of the seminal fluid that is released during ejaculation. The prostate gland is located beneath the bladder and surrounds the urethra. During the ejaculatory process, the gland releases an alkaline fluid into the urethra. There it is mixed with fluid from the seminal vesicles and spermatozoa from the testes to become the ejaculate.²

In BPH, as the prostate gland begins to enlarge, it may push against the urethra. Although not all men with an enlarged prostate experience symptoms, many of them do, particularly as the prostate increases in size. Patients with an enlarged prostate may present with lower urinary tract symptoms (LUTS) (TABLE 1). These LUTS tend to worsen over time as the gland gets increasingly larger.

During the first or early phase of BPH, the prostate tissue begins to hypertrophy. This may put pressure on the urethra, thus decreasing the size of the urethral lumen as a result of the mechanical obstruction. As the pressure increases, patients may experience difficulty initiating urination or may exhibit a weak or decreased stream. Some patients may even push on the bladder to initiate urination.

As symptoms worsen, bladder irritation may occur. This may denote the late phase of BPH. Urine remaining in the bladder may cause the organ to become hypersensitive. Even a small amount of residual urine, along with pressure from the enlarged prostate, may cause a patient to experience polyuria. It is important to remember that these symptoms may also be indicative of other disease states, such as prostatitis, prostate cancer, and urinary tract infection.The digital rectal examination (DRE) and the prostate-specific antigen (PSA) test are helpful for ruling out other conditions.¹

The American Urological Association (AUA) developed the Symptom Score Index (SSI) questionnaire to determine a baseline of BPH symptom severity and efficacy of treatment (TABLE 2). As the severity of LUTS increases, so does the SSI score. A score of 0 to 7 is termed mild; 8 to 19, moderate; 20 or greater, severe.² The seven-item questionnaire was designed for patient self-evaluation, but the practitioner may need to help the patient understand the terms. It is also recommended that, during the patient’s treatment plan, the same interviewer conduct the session so as to maintain a level of consistency.

It should be noted that the designations of mild, moderate, and severe BPH in the SSI are based on an arbitrarily assigned point system; therefore, they may not necessarily indicate how efficacious a given medication is. Instead, monitoring of the degree of decrease or increase in the score from baseline is considerably more reliable. Patients usually notice a “slight” or “moderate” improvement of their symptoms when the score decreases by three to four points or five to seven points, respectively.³

Treatment

The main goal of BPH therapy is to improve or relieve symptoms. Treatment is also aimed at halting disease progression and preventing the complications that may result from untreated BPH.⁴ Upon completion of the SSI, quality of life is the most important consideration when selecting an appropriate treatment option for a patient. A patient’s choice of therapy should take precedence. Therefore, the best possible treatment for a patient with mild symptoms and no complaints should include annual PSA and DRE monitoring, as well as directions to follow up if symptoms develop. The pharmacist counseling patients about BPH has an excellent opportunity to instruct them about lifestyle changes, including avoiding caffeine-containing beverages close to bedtime and taking diuretics in the morning instead of at night.

The treatment of LUTS associated with BPH is accomplished primarily with the use of two different drug classes: alpha-adrenergic antagonists (prazosin, terazosin, doxazosin, alfuzosin, and tamsulosin) and 5-alpha-reductase (5-AR) inhibitors (finasteride, dutasteride).⁵ Inhibition of alpha-adrenergic receptors prevents norepinephrine from binding to the alpha-adrenergic receptor, thereby facilitating a decrease in smooth-muscle tone in the prostate and urethra.⁶ Alpha-adrenergic antagonists have become first-line agents in the treatment of BPH due to their rapid onset of action and their proven safety and efficacy.⁷ It is important to note that they relax prostatic smooth muscle, but do not reduce prostate size.

Alpha-Adrenergic Antagonists: Adrenergic receptors were originally divided into alpha and beta subtypes, with alpha further classified into alpha-1 and alpha-2 receptors. Currently there are three subtypes in the alpha-1 subfamily: 1a, 1b, and 1d. Differences in receptor amino-acid sequence among these subtypes alter the binding properties of specific agonists and antagonists. In human prostate cells, the alpha-1a receptor type is the most prevalent type, making the targeting of this subtype therapeutically useful.⁶

The first generation of alpha-adrenergic antagonists (i.e., phenoxybenzamine) blocked both alpha-1 and alpha-2 receptors in the prostate and vasculature. Therefore, significant adverse events (e.g., orthostatic hypotension, reflex tachycardia, cardiac arrhythmias) limited their role in treating BPH, and they are no longer used.⁸

Second-generation alpha-adrenergic antagonists have a greater affinity for alpha-1 receptors than for alpha-2 receptors, leading to an improved side-effect profile. These second-generation agents include prazosin, terazosin, doxazosin, and alfuzosin. Despite the improvement over first-generation agents, these agents can still produce some hypotensive effects. These effects can be reduced by starting with a lower dose and slowly increasing the dose for several weeks, dosing at bedtime to reduce the incidence of syncope, and monitoring synergistic antihypertensive effects if given with other antihypertensive agents. Other common adverse events among the selective alpha-1 blockers include dizziness, asthenia, postural hypotension, syncope, headache, rhinitis, and sexual dysfunction.⁹ Dizziness and asthenia are the most frequently reported adverse effects.¹⁰

In a trial by Bozlu et al, the intensity of LUTS in 281 BPH patients with and without diabetes mellitus was evaluated, and the selective alpha-1 blockers (doxazosin, terazosin, alfuzosin, and tamsulosin) were studied to determine improvement of BPH symptoms in these patients.¹¹ Patients were treated for a minimum of six months. Diabetic patients with BPH had a greater improvement in BPH symptoms than nondiabetic patients (P <.01).¹¹

In a meta-analysis of placebo-controlled trials of 6,333 patients, terazosin, doxazosin, alfuzosin, and tamsulosin showed equal efficacy in improving voiding symptoms and increasing urinary flow rate. Rates of discontinuation and cardiovascular adverse events (i.e., first-dose syncope, orthostatic hypotension, and dizziness) were higher with terazosin, doxazosin, and immediate-release alfuzosin. Adverse events were lowest with extended-release alfuzosin and with tamsulosin, which had the lowest incidence of discontinuation and cardiovascular adverse events.^12,13 The AUA Practice Guidelines Committee has concluded that all agents in this class provided benefits in men with BPH by improving AUA Symptom Index (AUA-SI) scores by a mean of four to six points.¹⁴

Prazosin (Minipress) was the first second-generation alpha-adrenergic antagonist used to treat BPH. Although the medication is a selective alpha-1 antagonist, its utility in therapy is limited due to its relatively short half-life (2.5 hours), which requires multiple daily dosing (two to three times daily).⁶ Due to the number of doses required daily, compliance is a concern with this agent compared with terazosin and doxazosin.¹⁵ The AUA Practice Guidelines Committee states that data are insufficient to recommend the use of prazosin for the treatment of LUTS secondary to BPH.¹⁴ The variability in peak and trough serum levels of prazosin has led to a higher frequency of orthostatic hypotension, dizziness, and syncope. Other second-generation alpha-adrenergic antagonists also tend to cause hypotensive effects, however.⁸

Terazosin (Hytrin), also a selective alpha-1 adrenergic antagonist, has become the drug of choice for men with hypertension and BPH. The agent rarely causes sexual side effects. Common side effects of terazosin include dizziness, drowsiness, headache, constipation, loss of appetite, fatigue, nasal congestion, and dry eyes. Its relatively long half-life and low incidence of sexual side effects have led to wider use in the United States.⁶

Doxazosin (Cardura), a second-generation alpha blocker, is indicated for both hyper-tension and BPH. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT; 2000), the doxazosin arm was stopped early because it was less effective than the diuretic chlorthalidone (25% higher rate of cardiovascular disease and twice the rate of congestive heart failure vs. diuretics).^16,17 This suggests only that doxazosin should not be used as a primary antihypertensive agent.¹⁸

Alfuzosin (Uroxatral) is classified as an alpha-1 selective blocker. It produces a prostatic effect due to its extensive tissue distribution in the prostate.⁶ Alfuzosin relaxes muscles in the prostate and bladder neck, thereby easing urination. Common side effects of this medication are dizziness (postural hypotension), upper respiratory tract infection, headache, and fatigue.⁶ Less common side effects (0.6% to 7% of patients) include asthenia, fatigue, and abnormal ejaculation.^19,20 In one study, cardiovascular side effects with the 10-mg once-daily dose included blood-pressure changes.¹⁹ Another study, however, found that no changes in blood pressure have been observed thus far.²⁰

Alfuzosin should be used with caution in patients with renal insufficiency and should not be used in patients with a known history of QT prolongation. Because alfuzosin undergoes extensive hepatic metabolism, patients with liver failure should be initiated on the lowest daily dose and monitored for adverse effects.²¹ Cimetidine and diltiazem slow the hepatic metabolism of alfuzosin. Patients taking both alfuzosin and diltiazem should be monitored for increased serum levels of diltiazem.²²

Alfuzosin was compared with placebo in a pooled analysis of three parallel, randomized, double-blind, placebo-controlled, three-month trials. Patients received either 10 mg alfuzosin or placebo. The International Prostate Symptom Score (IPSS) and urinary peak flow rate (PFR) were significantly improved in the alfuzosin groups compared with placebo.¹⁹

In a comparison of immediate-release alfuzosin and prazosin (N = 103), both drugs were of comparable efficacy. The alfuzosin group had a lower incidence of cardiovascular (hypotension-related) effects, however.²³ Another comparison of immediate-release alfuzosin and tamsulosin (N = 256) revealed comparable efficacy in increasing PFR and reducing Boyarsky scores, as well as greater hypotensive effects in the alfuzosin group.²⁴ Adverse events such as dizziness, headache, palpitation, tachycardia, postural hypotension, syncope, and erectile dysfunction were similar between the two groups. One case of alfuzosin-associated dermatomyositis was reported, and severe, acute, mixed cholestatic, and hepatocellular-type hepatitis induced by alfuzosin were noted.^25,26

Tamsulosin (Flomax), a third-generation alpha-adrenergic antagonist, is a selective adrenergic-receptor blocker with high binding affinity for the alpha-1a and alpha-1d receptors.^8,27 This unique mechanism of action reduces the incidence of vascular effects by binding receptors predominantly present in the bladder.⁸ Due to its low affinity for vascular alpha-1 receptors, hypotension is not a common adverse effect.²⁸ This reduced vascular effect also provides greater flexibility in titration, where slow titration is no longer needed, unlike the second-generation agents. Concomitant use with antihypertensive agents does not pose a significant risk of hypotension.²⁹

A variety of adverse reactions have been reported with tamsulosin. This medication contains a sulfa moiety and therefore may cause typical sulfa reactions. Floppy-iris syndrome may be a concern for patients undergoing cataract surgery. Sexual dysfunction has been observed in patients taking tamsulosin. Studies have reported the occurrence of retrograde ejaculation (0.4 mg, 8.4%; 0.8 mg, 18.1%) and that ejaculatory disorders occurred more often with tamsulosin than with placebo (4.5% for 0.4 mg vs. 0.5% for placebo).^30-32 Vasodilatory side effects such as postural hypotension, seen with other alpha blockers, occur less frequently with tamsulosin.²

5-AR Inhibitors: Testosterone is converted to dihydrotestosterone (DHT) by 5-AR, which plays a major role in the normal development of prostate cells.³³ DHT is also associated with BPH, prostate cancer, and androgenic alopecia.³³ There are two isoforms of 5-AR: type 1 and type 2. Both isoforms are expressed in patients with BPH. Therefore, inhibiting both types would yield more significant results in the treatment of BPH.^34,35

Therapeutically, 5-AR inhibitors interfere with testosterone’s stimulatory effect on prostate enlargement, thereby making them effective for the reduction of symptom scores and the risk of acute urinary retention (AUR) and surgical intervention. However, drugs in this category require several months of treatment to achieve results.³⁶ The two agents in this class are finasteride and dutasteride.

Finasteride has been available in the U.S. for more than 10 years. It is marketed under two brand names: Proscar (indicated for the treatment of BPH) and Propecia (indicated for the treatment of alopecia). Finasteride is an antiandrogen, which acts on the type 2 reductase enzyme to reduce conversion of testosterone to DHT. Finasteride may be used in combination with doxazosin for the treatment of BPH.¹⁴ Importantly, because finasteride is a Pregnancy Category X medication, women who are or may become pregnant should not handle crushed or broken tablets. Exposure to whole tablets should not be harmful.³⁷

The four-year Proscar Long-Term Efficacy and Safety Study examined patients with BPH and enlarged prostate glands.³⁸ Patients received either finasteride 5 mg or placebo. The study found that there was a significant reduction in risk of urinary retention and surgery in patients treated with Proscar compared with placebo.³⁸ Additionally, two 12-month trials addressed the effect of daily doses of finasteride 1 mg to 5 mg and found a significant improvement in symptom scores and urinary PFR.^39,40

The PROWESS trial studied the long-term effects of finasteride 5 mg daily versus placebo in more than 3,000 BPH patients over two years.⁴¹ The primary endpoint was total symptom score on a modified Boyarsky questionnaire. Finasteride showed a greater, more significant improvement in total symptom score than placebo at four months and 24 months. Sexual side effects, including change in libido, ejaculation disorder, impotence, and orgasm dys-function, were experienced by 273 patients (165 in the finasteride group and 108 in the placebo group).⁴¹

A Canadian study evaluated LUTS secondary to BPH in 275 patients who received finasteride 5 mg as monotherapy for three months following nine months of finasteride combined with an alpha blocker.⁴² The primary endpoint was the change in IPSS upon cessation of the alpha blocker. The mean IPSS upon cessation of monotherapy was not significantly different from the nine-month IPSS after combination therapy; however, there was a statistically significant rise in IPSS from month 9 to month 12.⁴² The trial also found that the side-effect profile was similar between combination therapy and monotherapy. Thirty-one patients withdrew during the combination phase due to adverse events, and of the 220 patients who entered the monotherapy phase, 26 discontinued due to adverse events. The trial was completed by 107 patients. The most common reported nonserious adverse events (324) were decreased libido (5.2%), impaired urination (5.2%), urinary frequency (4.6%), decreased erection (3.7%), dizziness (3.1%), and decreased ejaculation (2.8%).⁴²

The PROSPECT study evaluated the use of finasteride in the treatment of moderate BPH over two years.⁴³ Patients (N = 613) were randomly assigned to receive placebo for one month, followed by either finasteride 5 mg daily or continued placebo. The primary endpoints were change in BPH symptoms, change in urinary flow rate, and change in prostate volume. The differences in symptom scores between the groups were most significant at 12 months and 16 months of therapy. Patients receiving finasteride showed marked improvement over placebo-treated patients. After two years, mean prostate volume was reduced by 21% in the finasteride group and increased by 8.4% in the placebo group; both values were statistically significant. More patients in the finasteride group experienced adverse sexual events (i.e., ejaculatory disorders and impotence), however.

Dutasteride (Avodart) is an oral synthetic 4-azasteroid.⁴⁴ It is a potent, selective, irreversible dual inhibitor of type 1 and type 2 5-AR.⁴⁴ The 0.5-mg tablet is dosed once daily for the treatment of moderate-to-severe BPH.⁴⁴ In clinical trials, dutasteride performed well in several key outcomes. During Phase II and Phase III trials, treatment of symptomatic BPH with dutasteride 0.5 mg once daily reduced serum DHT levels by 94% and 93.7%, respectively, compared with placebo.⁴⁴ In a dose-ranging study over 24 weeks, dutasteride 0.5 mg daily showed a greater reduction of serum DHT (95%) compared with finasteride 5 mg daily (71%; P <.001).⁴⁵ Additionally, three 2-year Phase III trials evaluated dutasteride 0.5 mg in more than 4,000 men. Statistically significant improvement with dutasteride versus placebo was observed in AUA-SI, total prostate volume (TPV), AUR, and need for surgical intervention.^46-51

The Enlarged Prostate International Comparator Study compared dutasteride with finasteride therapy over one year.⁵² Percentage change in TPV was the primary endpoint. TPV was decreased to the same degree (27.4%) by both dutasteride (0.5 mg daily) and finasteride (5 mg daily) after one year of therapy.⁵²

Dutasteride is extensively metabolized by the CYP450 isoenzymes 3A4 (CYP3A4) and 3A5; therefore, hepatic impairment may increase exposure to the drug. In vitro, co-administration of dutasteride with the CYP3A4 inhibitors verapamil, diltiazem, ritonavir, ketoconazole, cimetidine, troleandomycin, and ciprofloxacin reduced dutasteride clearance; this was not thought to be clinically significant, however.⁴⁵

In three trials with dutasteride 0.5 mg daily, the following adverse events occurred after 12 months of therapy: impotence (6%), decreased libido (3.7%), ejaculation disorder (1.8%), and gynecomastia (1.3%) for dutasteride compared with placebo (3%, 1.9%, 0.7%, and 0.5%, respectively).⁴⁶ The greater incidence of adverse sexual events recurred in comparison with placebo and included the following symptoms: impotence, decreased libido, and ejaculation disorder.^46,53,54 Gynecomastia has also been reported in other trials.^46,55

Combination Therapy: If the maximum titration of an alpha-1 receptor inhibitor does not yield significant relief of LUTS, a 5-AR inhibitor may be added. The Medical Therapy of Prostatic Symptoms (MTOPS) trial showed increased efficacy in relief of symptoms and reduction of disease progression when both classes were used, compared with either class alone.⁵⁶ Adverse effects are significantly increased, however, when the classes are used together. A benefit is most likely for patients with an enlarged prostate.²¹ Finally, if symptoms are moderate or severe despite maximum use of medications, surgery is an option that should be discussed with a urologist.⁷

The Symptom Management After Reducing Therapy trial involved combination therapy with dutasteride and tamsulosin followed by withdrawal of tamsulosin.⁵⁷ Patients were given either combination therapy (dutasteride 0.5 mg plus tamsulosin 0.4 mg) for 36 weeks or the same combination therapy for 24 weeks followed by dutasteride 0.5 mg plus placebo for 12 more weeks. The primary endpoint was comparison of change in urinary symptoms between weeks 24 and 30 in the two populations, based on patient response (improved or no change/worse). Ninety-one percent of the combination group reported no change or felt better at week 30, whereas 77% of the dutasteride-only group reported feeling the same or better.⁵⁷

More recent therapy management has focused on combination products—using both a 5-AR inhibitor and an alpha-adrenergic antagonist. Combination therapy with dutasteride and tamsulosin is currently being tested to measure efficacy against either therapy alone for treating symptoms and for long-term outcomes in men with moderate-to-severe LUTS and prostatic enlargement.⁵⁸ Patients are receiving one of the following therapies: dutasteride 0.5 mg, tamsulosin 0.4 mg, or combination therapy. The two-year interim report of the ongoing four-year trial currently shows that, in this patient population, combination therapy is of greater benefit than either therapy alone. Patients receiving the combination therapy also report adverse events similar to each monotherapy.⁴⁴ Although this trial is of interest, specifics cannot be drawn from it until the trial is completed.

One multicenter, randomized study showed no additive effect with a combination of terazosin and finasteride.⁵⁹ The 1,051 patients received extended-release alfuzosin (5 mg bid), finasteride (5 mg once daily), or both for six months. The data indicate that combination therapy with alfuzosin is not more efficacious than use of alfuzosin alone.⁶⁰

Prostate-specific antigen (PSA) is a known indicator of prostate size.⁵³ Treatment with dutasteride significantly reduced PSA by 50% in a Phase III trial, 57% in a four-year trial, and 55% in the two-year Combination of Avodart and Tamsulosin (CombAT) trial.^54,58,61 The primary endpoints in the CombAT trial were change in IPSS and risk of AUR or BPH-related surgery. IPSS was significantly more improved in the combination group, with a mean difference of −1.8 versus tamsulosin monotherapy and −1.3 versus dutasteride monotherapy after 24 months of therapy.⁵⁸

The reduction of DHT in patients taking 5-AR inhibitors (i.e., dutasteride and finasteride) has been shown to reduce mean semen volume and sperm motility compared with placebo.⁶² Spermatogenesis indicators returned to baseline levels 20 to 24 weeks after the end of the trial and cessation of the agents.⁶² The CombAT trial revealed a higher adverse-event occurrence for combination therapy (24%) compared with monotherapy with dutasteride (18%) and tamsulosin (16%).⁵⁸ A review article concluded that patients who would receive the most benefit from combination of a 5-AR inhibitor and an alpha-1 adrenergic-receptor antagonist were those with a large prostate, severe symptoms, and high PSA levels.³⁶

The four-year MTOPS trial examined the effects of doxazosin, finasteride, combination therapy, and placebo on the composite endpoint of BPH progression (i.e., ≥4-point increase in AUA-SI from baseline, AUR, urinary incontinence, renal insufficiency, recurrent urinary tract infection).⁵⁶ There was a significant progression risk reduction in all treatment groups compared with placebo; however, progression risk reduction was greater for combination therapy (66%) compared with either form of monotherapy (doxazosin, 39%; finasteride, 34%). The finasteride group had a significantly greater occurrence of erectile dysfunction compared with the placebo group. The doxazosin group had greater incidences of dizziness, postural hypotension, and asthenia compared with the placebo group. Combination therapy had a greater occur-rence of all the aforementioned adverse events compared with the placebo group.⁷

The Prospective European Doxazosin and Combination Therapy (PREDICT) trial evaluated doxazosin, finasteride, and the combination for one year. IPSS and urinary PFR were the primary endpoints of the trial. Patients receiving doxazosin and those receiving combination therapy showed significant improvements in IPSS and urinary PFR compared with the finasteride group. There was no difference between the doxazosin and combination-therapy groups, however.⁶³

ALLHAT revealed some intriguing results with second-generation alpha-1 receptor inhibitors.¹⁸ The doxazosin arm was discontinued early because the drug did not reduce coronary heart disease or total mortality in patients with hypertension and there was an 80% increased risk of developing heart failure. Therefore, second-generation alpha-1 receptor inhibitors should not be used for the dual treatment of BPH and hypertension. Additional antihypertensives with doxazosin or terazosin are recommended for patients with both disease states.

The third-generation alpha-1 receptor inhibitors, tamsulosin and alfuzosin, are uroselective because they act on prostate tissue without decreasing blood pressure. Thus, they are not FDA-approved for hypertension. Tamsulosin is available in doses of 0.4 mg, and alfuzosin is available in doses of 10 mg. Both drugs are dosed once daily, but they should be given after the same meal each day rather than at bedtime. Also, they relieve symptoms more quickly (one day for onset and one week for peak relief ) than the second-generation alpha-1 receptor inhibitors.⁷ Waiting two to four weeks after starting these medications to evaluate their efficacy ensures a peak response, however. Adverse effects of tamsulosin and alfuzosin include dizziness, asthenia, and, in the case of tamsulosin, abnormal ejaculation.¹⁹

Conclusion

The impact of untreated or undertreated BPH and its symptoms on quality of life is enormous. Patients presenting with symptoms should have a baseline SSI assessed. The baseline can then be compared with subsequent scores throughout therapy. Appropriate medication therapy and significant reduction in LUTS can greatly improve a patient’s quality of life. For most patients, this can be realized with an appropriate agent and vigilant, regular examinations.

For moderate symptoms, BPH medications usually are preferred, including alpha-1 receptor inhibitors and 5-AR inhibitors. Alpha-1 receptor inhibitors decrease smooth-muscle tone in the prostate tissue, bladder neck, and urethra. This action is quick compared with that of 5-AR inhibitors, making them the drugs of choice for patients needing immediate symptom relief. As a final alternative, surgery may be required in severe cases. The pharmacist is in a unique position to address patients’ concerns about prostate health and should encourage hesitant patients to ask any questions they may have.

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